Orexins increase penicillin-induced epileptic activity

Kortunay, Selim; Erken, Haydar Ali; Erken, Gülten; Genç, Osman; Şahiner, Melike; Turgut, Sebahat; Turgut, Günfer

doi:10.1016/j.peptides.2012.02.013

Cited by 30 publications

(18 citation statements)

References 33 publications

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“…Orexin receptors and possibly orexin synthesis are present in the hippocampus, a region of great importance for temporal lobe epilepsy (Marcus et al, 2001;Morales et al, 2006). Previously, a link between DAG and the orexin pathway was shown in relation to feeding (Toshinai et al, 2006) and the orexin family seems to be involved in epileptic mechanisms (Akbari et al, 2014;Akdogan et al, 2008;Doreulee et al, 2010;Erken et al, 2012;Kortunay et al, 2012;Rejdak et al, 2009). It is thought that orexin release in the hippocampus may be excitatory (Akbari et al, 2011;Ida et al, 1999;Selbach et al, 2004;Wayner et al, 2004).…”

Section: Article In Pressmentioning

confidence: 99%

Des-acyl ghrelin attenuates pilocarpine-induced limbic seizures via the ghrelin receptor and not the orexin pathway

et al. 2015

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Section: Article In Pressmentioning

confidence: 99%

Des-acyl ghrelin attenuates pilocarpine-induced limbic seizures via the ghrelin receptor and not the orexin pathway

et al. 2015

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“…For example, it was reported that intracortical and intracerebroventricular injections of orexins caused seizure-related behaviors in rats [ 15 , 16 ]. Both orexin A and B enhanced the excitability of the central nervous system following administration of penicillin G [ 17 ]. In accordance, it was revealed that during pilocarpine-induced epileptic activity, the expression of orexin B was increased in the rat hippocampus [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

The effect of intracerebroventricular administration of orexin receptor type 2 antagonist on pentylenetetrazol-induced kindled seizures and anxiety in rats

et al. 2018

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BackgroundCurrent antiepileptic drugs are not able to prevent recurrent seizures in all patients. Orexins are excitatory hypothalamic neuropeptides that their receptors (Orx1R and Orx2R) are found almost in all major regions of the brain. Pentylenetetrazol (PTZ)-induced kindling is a known experimental model for epileptic seizures. The purpose of this study was to evaluate the effect of Orx2 receptor antagonist (TCS OX2 29) on seizures and anxiety of PTZ-kindled rats.ResultsOur results revealed that similar to valproate, administration of 7 µg/rat of TCS OX2 29 increased the latency period and decreased the duration time of 3rd and 4th stages of epileptiform seizures. Besides, it significantly decreased mean of seizure scores. However, TCS OX2 29 did not modulate anxiety induced by repeated PTZ administration.ConclusionThis study showed that blockade of Orx2 receptor reduced seizure-related behaviors without any significant effect on PTZ-induced anxiety.

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“…Erken et al [10] also reported that intracortical injection of orexins (A or B) caused seizures. They also showed that ICV injection of orexins enhanced penicillin-induced epileptic activity [11]. A recent study showed that following maximal electroshock seizure and intravenous injection of PTZ, the orexin-A concentration in the brain was elevated for up to 4 h following the seizure [21].…”

Section: Discussionmentioning

confidence: 99%

SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats

Jaz

Moghimi

Fereidoni

et al. 2016

Fundam Clin Pharmacol

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Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin-A and orexin-B are brain neuropeptides originating from postero-lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist (SB-334867) on seizure- and anxiety-related behaviors of pentylenetetrazol (PTZ)-kindled rats. Kindling was induced by repeated intraperitoneal (IP) injections of PTZ (32 mg/kg) with two-day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular (ICV) injections of SB-334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure-related behaviors were monitored for 30 min following PTZ administration. The anxiety-like behaviors were also assessed using elevated plus-maze in the first and last days of the study. The results revealed that ICV injection of SB-334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ-induced anxiety-like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders.

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Orexins increase penicillin-induced epileptic activity

Cited by 30 publications

References 33 publications

Des-acyl ghrelin attenuates pilocarpine-induced limbic seizures via the ghrelin receptor and not the orexin pathway

Des-acyl ghrelin attenuates pilocarpine-induced limbic seizures via the ghrelin receptor and not the orexin pathway

The effect of intracerebroventricular administration of orexin receptor type 2 antagonist on pentylenetetrazol-induced kindled seizures and anxiety in rats

SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats

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